Clinical analyzers that automatically perform chemical assays and immunoassays of biological fluids such as urine, blood serum, plasma, cerebrospinal liquids and the like are in widespread commercial use. Generally, chemical reactions between an analyte in a patient sample and reagents used during analysis generate some sort of signal that can be measured by the analyzer. The concentration of analyte in the patient sample may be determined from this signal.
Clinical analyzers generally use aspirating means such as a hollow sampling probe or needle to transfer predetermined volumes of liquid samples or liquid reagents between receptacles, such as between sample containers, reagent containers and reaction cuvettes disposed on the analyzer. The aspirating means typically includes an elongated, needle-like pipette member having a hollow passage whereby liquid may be aspirated into and/or dispensed from the sample probe. The pipette is carried by a transport mechanism conventionally adapted to provide horizontal and vertical movement enabling the pipette tip to be lowered into a liquid for aspiration of the liquid, and for transporting the liquid to a site whereat the pipette is lowered to an optimal position for dispensing the liquid into another container. Some type of aspirating means, such as a piston and/or vacuum assembly, is controlled to aspirate liquid into the pipette and to dispense liquid from the pipette. Hereinafter, variations of the term aspirate refer to all of such processes for extracting liquid from one container and depositing at least some of the liquid into the same or another container and further includes the supporting devices required to complete the liquid handling operations.
U.S. Pat. No. 4,794,085 describes a method which permits the detection of penetration of liquid by an apertured container used for aspirating and dispensing the liquid. The apparatus has control means for advancing the container an increment of the maximum possible distance to the liquid, means to generate a pressure differential within the dispensing container that is sufficient to generate a signal that is indicative of whether the container aperture is closed by the liquid, and devices to detect and signal the pressure produced within the container by such a pressure differential.
U.S. Pat. No. 4,926,701 describes a pipetting device comprising a probe for dipping into a reservoir, reaction vessel or the like, a metering pump connected to the probe and a shutoff valve disposed between the probe and the pump are provided. In the intake phase of the pump with the valve open, first air and then a predetermined quantity of liquid is taken in.
U.S. Pat. No. 4,951,512 provides for providing access to a sealed container which temporarily provides an opening in the closures of the containers, and either removes contents, senses properties of the contents, or dispenses material into the container. A lift assembly moves each sample container upward against a puncture tube to produce an opening in the closure of the container. The system takes a sample through this opening or inserts a probe through the opening to measure the properties of the sample.
U.S. Pat. No. 5,163,582 covers an apparatus and method for dispensing a predetermined volume of liquid from a closed, liquid-containing blood collection tube. The apparatus includes a dual conduit providing a passageway for liquid to be dispensed from a closed blood collection tube and a gas conduit providing a passageway for gas to be introduced into the blood collection tube. Included in the apparatus is insertion of the dual conduit into the blood collection tube, turning the tube away from a vertical, upright orientation, connecting and disconnecting the gas passageway from a gas supply, displacing a volume of gas through the gas passageway, and controlling the operation of the apparatus.
U.S. Pat. No. 5,413,246 discloses a disposable apparatus to dispense an amount of liquid from a closed container using a stopper piercing means to access the interior of a closed blood collection tube, a gas passage means to allow a metered amount of gas to be forced into the blood collection tube, and a liquid passage means to allow fluid to be dispensed from the tube in proportion to the amount of gas forced into the tube.
U.S. Pat. No. 5,499,545 is a method for improving measurement accuracy by eliminating the influence of changes in the atmospheric and internal pressures on the quantity of a liquid absorbed or discharged. A pipetting device inducts a specified quantity of liquid into a tip portion or discharges a specified quantity of liquid from the tip portion by controlling the pressure inside a cylinder portion including a cylinder and a piston.
From the above art, it is evident that much attention has been given to extracting liquid samples from containers, without addressing another critical factor in obtaining accurate analytical measurements, that being aspiration of a uniform and representative aliquot portion of a patient sample from a sample container. This is an especially critical factor when the liquid to be analyzed is one of several body fluids as these frequently have a non-uniform composition. In particular, when the sample to be analyzed is a sample of whole blood that has not been preprocessed, a natural sedimentation occurs during a 30 minute period after the sample has been mixed, for instance by inversion of a primary whole blood tube. To compensate for such sedimentation, automated analyzers may be adapted with an automatic mixing mechanism, thereby adding complexity and cost as well as decreasing the reliability of an analyzer.